Hypercapnic acidosis does not modulate the severity of bacterial pneumonia–induced lung injury

O’Croinin, Donall; Hopkins, Natalie; Moore, Michael J.; Boylan, John F.; McLoughlin, Paul; Laffey, John G.

doi:10.1097/01.ccm.0000186761.41090.c6

Cited by 47 publications

(48 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By contrast, studies on the effects of hypercapnia during bacterial pulmonary infection in rats have produced highly variable results (17)(18)(19)(20)(21). In those reports, lung injury parameters and bacterial burden, as assessed in anesthetized and mechanically ventilated animals after intratracheal inoculation with Escherichia coli, were variously unaffected, worsened, or attenuated by hypercapnia.…”

mentioning

confidence: 87%

“…As already noted, another group has studied the impact of hypercapnia in a rat model of pulmonary infection with E. coli, finding alternately deleterious or beneficial effects using a variety of protocols in multiple reports (17)(18)(19)(20)(21). In all but one of these, the effects of hypercapnia were evaluated exclusively in anesthetized animals undergoing mechanical ventilation over a period of 4 to 6 hours.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Hypercapnia Impairs Lung Neutrophil Function and Increases Mortality in Murine Pseudomonas Pneumonia

Gates

Howell²,

Nair

et al. 2013

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Hypercapnia, an elevation of the level of carbon dioxide (CO 2 ) in blood and tissues, is a marker of poor prognosis in chronic obstructive pulmonary disease and other pulmonary disorders. We previously reported that hypercapnia inhibits the expression of TNF and IL-6 and phagocytosis in macrophages in vitro. In the present study, we determined the effects of normoxic hypercapnia (10% CO 2 , 21% O 2 , and 69% N 2 ) on outcomes of Pseudomonas aeruginosa pneumonia in BALB/c mice and on pulmonary neutrophil function. We found that the mortality of P. aeruginosa pneumonia was increased in 10% CO 2 -exposed compared with air-exposed mice. Hypercapnia increased pneumonia mortality similarly in mice with acute and chronic respiratory acidosis, indicating an effect unrelated to the degree of acidosis. Exposure to 10% CO 2 increased the burden of P. aeruginosa in the lungs, spleen, and liver, but did not alter lung injury attributable to pneumonia. Hypercapnia did not reduce pulmonary neutrophil recruitment during infection, but alveolar neutrophils from 10% CO 2 -exposed mice phagocytosed fewer bacteria and produced less H 2 O 2 than neutrophils from air-exposed mice. Secretion of IL-6 and TNF in the lungs of 10% CO 2 -exposed mice was decreased 7 hours, but not 15 hours, after the onset of pneumonia, indicating that hypercapnia inhibited the early cytokine response to infection. The increase in pneumonia mortality caused by elevated CO 2 was reversible when hypercapnic mice were returned to breathing air before or immediately after infection. These results suggest that hypercapnia may increase the susceptibility to and/or worsen the outcome of lung infections in patients with severe lung disease.Keywords: carbon dioxide; pulmonary infection; reactive oxygen species; phagocytosis; inflammation Hypercapnia occurs in patients with severe acute and chronic lung diseases such as chronic obstructive pulmonary disease (COPD), currently the third leading cause of death in the United States (1). Individuals with COPD and other chronic respiratory disorders are also at risk for the development of acute respiratory failure, which may be accompanied by acute or acute-on-chronic hypercapnia. In addition, patients with acute respiratory distress syndrome (ARDS) and status asthmaticus may develop hypercapnia.Hypercapnia has long been recognized as a marker of poor prognosis in patients with COPD, among whom pulmonary infections are a major cause of morbidity and mortality (2-6). Hypercapnia is also an independent risk factor for mortality in hospitalized patients with community-acquired pneumonia and in patients with cystic fibrosis awaiting lung transplantation (7-10). Moreover, hypercapnic patients with acute respiratory failure can develop ventilatorassociated pneumonia, which prolongs intensive care unit and hospital stays, and carries a mortality rate of 33-50% (11). On the other hand, in some studies, hypercapnia accompanying low tidal volume mechanical ventilation ("permissive hypercapnia") has been associated with reduced mor...

show abstract

mentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Hypercapnia Impairs Lung Neutrophil Function and Increases Mortality in Murine Pseudomonas Pneumonia

Gates

Howell²,

Nair

et al. 2013

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

show abstract

“…Immediately postmortem, the heart-lung block was removed and bronchoalveolar lavage (BAL) carried out. 23,24 BAL differential cell counts were performed. BAL protein was measured using a Micro BCA TM Protein assay kit (Pierce, Rockford, IL).…”

Section: Lung Injury and Repair Assessmentmentioning

confidence: 99%

“…27 The left lung was fixed using paraformaldehyde, and histologic lung injury assessed using quantitative stereology. 23,27 The investigator performing the physiologic assessment was not blinded to group allocation; however, the investigators were blinded for all other assessments and assays. …”

mentioning

confidence: 99%

Effects of Intratracheal Mesenchymal Stromal Cell Therapy during Recovery and Resolution after Ventilator-induced Lung Injury

et al. 2013

Self Cite

View full text Add to dashboard Cite

Background: Mesenchymal stromal cells (MSCs) have been demonstrated to attenuate acute lung injury when delivered by intravenous or intratracheal routes. The authors aimed to determine the efficacy of and mechanism of action of intratracheal MSC therapy and to compare their efficacy in enhancing lung repair after ventilation-induced lung injury with intravenous MSC therapy. Methods: After induction of anesthesia, rats were orotracheally intubated and subjected to ventilation-induced lung injury (respiratory rate 18 min −1 , P insp 35 cm H 2 O,) to produce severe lung injury. After recovery, animals were randomized to receive: (1) no therapy, n = 4; (2) intratracheal vehicle (phosphate-buffered saline, 300 µl, n = 8); (3) intratracheal fibroblasts (4 × 10 6 cells, n = 8); (4) intratracheal MSCs (4 × 10 6 cells, n = 8); (5) intratracheal conditioned medium (300 µl, n = 8); or (6) intravenous MSCs (4 × 10 6 cells, n = 4). The extent of recovery after acute lung injury and the inflammatory response was assessed after 48 h. Results: Intratracheal MSC therapy enhanced repair after ventilation-induced lung injury, improving arterial oxygenation (mean ± SD, 146 ± 3.9 vs. 110.8 ± 21.5 mmHg), restoring lung compliance (1.04 ± 0.11 vs. 0.83 ± 0.06 ml·cm H 2 O −1 ), reducing total lung water, and decreasing lung inflammation and histologic injury compared with control. Intratracheal MSC therapy attenuated alveolar tumor necrosis factor-α (130 ± 43 vs. 488 ± 211 pg·ml −1) and interleukin-6 concentrations (138 ± 18 vs. 260 ± 82 pg·ml −1 ). The efficacy of intratracheal MSCs was comparable with

show abstract

“…Intriguingly, these protective eff ects were mediated by a mechanism indepen dent of neutrophil function. In contrast, hypercapnic acidosis did not alter the magnitude of lung injury in a less severe acute bacterial pneumonia [39]. Importantly these in vivo studies showed no increase in bacterial count in animals exposed to hypercapnic acidosis, a reassuring fi nding given concerns regarding retardation of the host bactericidal response and potential bacterial proliferation.…”

Section: Early Lung Infectionmentioning

confidence: 73%

Can ‘Permissive’ Hypercapnia Modulate the Severity of Sepsis-induced ALI/ARDS?

Curley

Hayes

Laffey

2011

Annual Update in Intensive Care and Emergency Medicine 2011

View full text Add to dashboard Cite

Ventilatory strategies that reduce lung stretch by reducing tidal and minute ventilation, which results in a 'permissive' hypercapnic acidosis, improve outcome in patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) [1,2]. Reassuringly, evidence from clinical studies attests to the safety and lack of detrimental eff ects of hypercapnic acidosis [2]. Of parti cu lar importance, a secondary analysis of data from the ARDSnet tidal volume study [1] demonstrated that the presence of hypercapnic acidosis at the time of randomization was associated with improved patient survival in patients who received high tidal volume ventilation [3]. Th ese fi ndings have resulted in a shift in paradigms regarding hypercapnia -from avoidance to tolerancewith hypercapnia increasingly permitted in order to realize the benefi ts of low lung stretch. Conse quently, low tidal and minute volume ventilation and the accompanying `permissive' hypercapnia are now the standard of care for patients with ALI/ARDS, and are increasingly used in the ventilatory management of a diverse range of diseases leading to acute severe respira tory failure, includ ing asthma and chronic obstructive pulmonary disease.Th e infl ammatory response plays a central role in the pathogenesis of injury and in the repair process in ALI/ ARDS [4]. Infl ammation is a highly conserved process in evolution, which is essential for survival. It functions to resolve the injurious process, facilitate repair, and return the host to a state of homeostasis. Th e ideal infl ammatory process is rapid, causes focused destruction of pathogens, yet is specifi c and ultimately self-limiting [5]. In contrast, when the infl ammatory response is dysregulated or persistent, this can lead to excessive host damage, and contribute to the pathogenesis of lung and systemic organ injury, leading to multiple organ failure and death. Th e potential for hypercapnia and/or its associated acidosis to potently inhibit the immune response is increasingly recognized [6,7]. Where the host immune response is a major contri bu tor to injury, such as in non-septic ALI/ ARDS, these eff ects would be expected to result in potential benefi t. Th is has been demonstrated clearly in relevant pre-clinical ALI/ARDS models, where hypercapnic acidosis has been demonstrated to attenuate ALI induced by free radicals [8], pulmonary [9] and systemic ischemia-reperfusion [10], pulmonary endo toxin instillation [11], and excessive lung stretch [12]. Th e protective eff ects of hypercapnic acidosis in these models appear due, at least in part, to its anti-infl ammatory eff ects.Th e eff ects of hypercapnia in sepsis-induced lung injury, where a robust immune response to microbial infec tion is central to bacterial clearance and recovery, is less clear. Of concern, severe sepsis-induced organ failure, whether pulmonary or systemic in origin, is the leading cause of death in critically ill adults and children [13]. Sepsis-induced ARDS is associated with the highest mortality rates. Evidence sugges...

show abstract

Hypercapnic acidosis does not modulate the severity of bacterial pneumonia–induced lung injury

Abstract: We conclude that hypercapnic acidosis did not alter the magnitude of the lung injury induced by intratracheal E. coli instillation in the presence or absence of antibiotics.

Cited by 47 publications

References 42 publications

Hypercapnia Impairs Lung Neutrophil Function and Increases Mortality in Murine Pseudomonas Pneumonia

Hypercapnia Impairs Lung Neutrophil Function and Increases Mortality in Murine Pseudomonas Pneumonia

Effects of Intratracheal Mesenchymal Stromal Cell Therapy during Recovery and Resolution after Ventilator-induced Lung Injury

Can ‘Permissive’ Hypercapnia Modulate the Severity of Sepsis-induced ALI/ARDS?

Contact Info

Product

Resources

About